Body composition assessment of people with overweight/obesity with a simplified magnetic resonance imaging method.

To develop a simplified magnetic resonance imaging method (MRI) to assess total adipose tissue (AT) and adipose tissue free mass (ATFM) from three single MRI slices in people with overweight/obesity in order to implement body composition follow-up in a clinical research setting. Body composition of 310 participants (70 women and 240 men, age: 50.8 ± 10.6 years, BMI: 31.3 ± 5.6 kg.m-2) was assessed with 3 single slices (T6-T7, L4-L5 and at mid-thigh) MRI. Multiple regression analysis was used to develop equations predicting AT and ATFM from these three single slices. Then we implemented a longitudinal phase consisting in a 2-month exercise training program during which we tested the sensitivity of these equations in a subgroup of participants with overweight/obesity (n = 79) by comparing the exercise-induced variations between predicted and measured AT and ATFM. The following equations: total AT = - 12.74105 + (0.02919 × age) + (4.27634 × sex (M = 0, F = 1)) + (0.22008 × weight) + (26.92234 × AT T6-T7) + (23.70142 × AT L4-L5) + (37.94739 × AT mid-thigh) and total ATFM = - 33.10721 + (- 0.02363 × age) + (- 3.58052 × sex (M = 0, F = 1)) + (30.02252 × height) + (0.08549 × weight) + (11.36859 × ATFM T6-T7) + (27.82244 × ATFM L4-L5) + (58.62648 × ATFM mid-thigh) showed an excellent prediction (adjusted R2 = 97.2% and R2 = 92.5%; CCC = 0.986 and 0.962, respectively). There was no significant difference between predicted and measured methods regarding the AT variations (- 0.07 ± 2.02 kg, p = 0.70) and the ATFM variations (0.16 ± 2.41 kg, p = 0.49) induced by 2-months of exercise training. This simplified method allows a fully accurate assessment of the body composition of people with obesity in less than 20 min (10 min for images acquisition and analysis, respectively), useful for a follow-up.

High-intensity interval training to promote cerebral oxygenation and affective valence during exercise in individuals with obesity.

Left/right prefrontal cortex (PFC) activation is linked to positive/negative affects, respectively. Besides, larger left PFC oxygenation during exercise relates to higher cardiorespiratory fitness (CRF). High-intensity interval training (HIIT) is superior to moderate-intensity continuous training (MICT) in improving CRF. The influence of training on PFC oxygenation and affects during exercise in individuals with obesity is, however, currently unknown. Twenty participants with obesity (14 males, 48 ± 8 years, body-mass index = 35 ± 6 kg·m-2) were randomised to MICT [50% peak work rate (WRpeak)] or HIIT (1-min bouts 100% WRpeak; 3 sessions/week, 8 weeks). Before/after training, participants completed an incremental ergocycle test. Near-infrared spectroscopy and the Feeling Scale assessed PFC oxygenation and affects during exercise, respectively. Improvements in CRF (e.g., WRpeak: 32 ± 14 vs 20 ± 13 W) were greater after HIIT vs MICT (p < 0.05). Only HIIT induced larger left PFC oxygenation (haemoglobin difference from 7 ± 6 to 10 ± 7 µmol) and enhanced affective valence (from 0.7 ± 2.9 to 2.2 ± 2.0; p < 0.05) at intensities ≥ second ventilatory threshold. Exercise-training induced changes in left PFC oxygenation correlated with changes in CRF [e.g., WRpeak (% predicted), r = 0.46] and post-training affective valence (r = 0.45; p < 0.05). HIIT specifically improved left PFC oxygenation and affects during exercise in individuals with obesity. Implementing HIIT in exercise programmes may therefore have relevant implications for the management of obesity, since greater affective response to exercise is thought to be associated with future commitment to physical activity.

Nocturnal hypoxemia, blood pressure, vascular status and chronic mountain sickness in the highest city in the world.

INTRODUCTION: Chronic mountain sickness (CMS) is a condition characterized by excessive erythrocytosis in response to chronic hypobaric hypoxia. CMS frequently triggers cardiorespiratory diseases such as pulmonary hypertension and right or left heart failure. Ambient hypoxia might be further amplified night-time by intermittent hypoxia related to sleep-disordered breathing (SDB) so that sleep disturbance may be an important feature of CMS. Our aim was to characterize in a cross-sectional study nocturnal hypoxaemia, SDB, blood pressure (BP), arterial stiffness and carotid intima-media thickness (CIMT) in highlanders living at extreme altitude. METHODS: Men aged 18 to 55 years were prospectively recruited. Home sleep apnoea test, questionnaires (short-form health survey; Montreal cognitive assessment; Pittsburgh Sleep Questionnaire Index and the Insomnia severity index), 24-h ambulatory BP monitoring, CIMT and arterial stiffness were evaluated in 3 groups: i) Andean lowlanders (sea-level); ii) highlanders living at 3,800 m and iii) highlanders living at 5,100 m. Analyses were conducted in sub-groups according to 1) CMS severity 2) healthy subjects living at the three different altitude. RESULTS: Ninety-two males were evaluated at their living altitudes. Among the 54 highlanders living at 5,100 m, subjects with CMS showed lower mean nocturnal oxygen saturation (SpO2), SpO2 nadir, lower pulse wave velocity and higher nocturnal BP variability than those with no-CMS. Lower nocturnal SpO2 nadir was associated with higher CMS severity (ß= -0.14, p=.009). Among the 55 healthy subjects, healthy highlanders at 5,100 m were characterized by lower scores on quality of life and sleep quality scales and lower mean SpO2 compared to lowlanders. CONCLUSIONS: Lower nocturnal SpO2 and higher nocturnal BP variability are associated with CMS severity in individuals living permanently at high altitude. The role of lower SpO2 and higher nocturnal BP variability in the cardiovascular progression of CMS and in the overall prognosis of the disease need to be evaluated in further studies.

Toward Neuro-Oncologic Clinical Trials of High-Dose-Rate Synchrotron Microbeam Radiation Therapy: First Treatment of a Spontaneous Canine Brain Tumor.

PURPOSE: The high potential of microbeam radiation therapy (MRT) in improving tumor control while reducing side effects has been shown by numerous preclinical studies. MRT offers a widened therapeutic window by using the periodical spatial fractionation of synchrotron generated x-rays into an array of intense parallel microbeams. MRT now enters a clinical transfer phase. As proof of principle and cornerstone for the safe clinical transfer of MRT, we conducted a "first in dog" trial under clinical conditions. In this report, we evaluated whether a 3-dimensional conformal MRT can be safely delivered as exclusive radiosurgical treatment in animal patients METHODS AND MATERIALS: We irradiated a 17.5-kg French bulldog for a spontaneous brain tumor (glioma suspected on magnetic resonance imaging) with conformal high-dose-rate microbeam arrays (50-µm-wide microbeams, replicated with a pitch of 400 µm) of synchrotron-generated x-rays. The dose prescription adjusted a minimal cumulated valley dose of 2.8 Gy to the plnning target volume (PTV) (cinical target volume (CTV)+ 1 mm). Thus, each beam delivered 20 to 25 Gy to the target as peak doses, and ∼1 Gy as valley doses RESULTS: The treatment was successfully delivered. Clinical follow-up over 3 months showed a significant improvement of the dog's quality of life: the symptoms disappeared. Magnetic resonance imaging, performed 3 months after irradiation, revealed reduction in tumor size (-87.4%) and mass effect with normalization of the left lateral ventricle. CONCLUSIONS: To our knowledge, this neuro-oncologic veterinary trial is the first 3-dimensional conformal synchrotron x-ray MRT treatment of a spontaneous intracranial tumor in a large animal. It is an essential last step toward the clinical transfer of MRT in the near future to demonstrate the feasibility and safety of treating deep-seated tumors using synchrotron-generated microbeams.

Effects of high intensity interval training on sustained reduction in cardiometabolic risk associated with overweight/obesity. A randomized trial.

Background: Considering the potential greater cardiocirculatory effects of high intensity interval training (HIIT), we hypothesized that a 2-month supervised high volume short interval HIIT would induce greater improvements in CRF and cardiometabolic risk and increase long-term maintenance to physical activity compared to isocaloric moderate intensity continuous training (MICT) in overweight/obesity. Methods: Sixty (19 females) subjects with overweight/obesity were randomized to three training programs (3 times/week for 2 months): MICT (45 min, 50% peak power output-PPO), HIIT (22 × 1-min cycling at 100% PPO/1-min passive recovery) and HIIT-RM (RM: recovery modulation, i.e. subjects adjusted passive recovery duration between 30s and 2 min). After the intervention, participants no longer benefited from supervised physical activity and were instructed to maintain the same exercise modalities on their own. We assessed anthropometrics, body composition, CRF, fat oxidation, lipid profile, glycemic balance, low-grade inflammation, vascular function, spontaneous physical activity and motivation for eating at three time points: baseline (T0), 4 days after the end of the 2-month supervised training program (T2) and 4 months after the end of the training program (T6). Results: HIIT/HIIT-RM induced greater improvement in VO2peak (between +14% and +17%), power output at ventilatory thresholds and at maximal fat oxidation rate (+25%) and waist circumference (-1.53 cm) compared to MICT and tended to decrease insulin resistance. During the four-month follow-up period during which exercise in autonomy was prescribed, HIIT induced a greater preservation of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL. Conclusion: We have shown greater short-term benefits induced by a high volume short interval (1 min) HIIT on cardiorespiratory fitness and cardiometabolic risk over an isocaloric moderate intensity continuous exercise in persons with overweight/obesity. We also showed greater long-term effects (i.e. after 4 months) of this exercise modality on the maintenance of CRF, decreases in total and abdominal fat masses and total cholesterol/HDL.

MEDEX 2015: Prophylactic Effects of Positive Expiratory Pressure in Trekkers at Very High Altitude.

Purpose: Positive expiratory pressure (PEP) breathing has been shown to increase arterial oxygenation during acute hypoxic exposure but the underlying mechanisms and consequences on symptoms during prolonged high-altitude exposure remain to be elucidated. Methods: Twenty-four males (41 ± 16 years) were investigated, at sea level and at 5,085 m after 18 days of trekking from 570 m. Participants breathed through a face-mask with PEP = 0 cmH2O (PEP0, 0-45th min) and with PEP = 10 cmH2O (PEP10, 46-90th min). Arterial (SpO2), quadriceps and prefrontal (near infrared spectroscopy) oxygenation was measured continuously. Middle cerebral artery blood velocity (MCAv, transcranial Doppler), cardiac function (2D-echocardiography), extravascular lung water accumulation (UsLC, thoracic ultrasound lung comets) and acute mountain sickness (Lake Louise score, LLS) were assessed during PEP0 and PEP10. Results: At 5,085 m with PEP0, SpO2 was 78 ± 4%, UsLC was 8 ± 5 (a.u.) and the LLS was 2.3 ± 1.7 (all P < 0.05 versus sea level). At 5,085 m, PEP10 increased significantly SpO2 (+9 ± 5%), quadriceps (+2 ± 2%) and prefrontal cortex (+2 ± 2%) oxygenation (P < 0.05), and decreased significantly MCAv (-16 ± 14 cm.s-1) and cardiac output (-0.7 ± 1.2 L.min-1) together with a reduced stroke volume (-9 ± 15 mL, all P < 0.05) and no systemic hypotension. PEP10 decreased slightly the number of UsLC (-1.4 ± 2.7, P = 0.04) while the incidence of acute mountain sickness (LLS ≥ 3) fell from 42% with PEP0 to 25% after PEP10 (P = 0.043). Conclusion: PEP10 breathing improved arterial and tissue oxygenation and symptoms of acute mountain sickness after trekking to very high altitude, despite reduced cerebral perfusion and cardiac output. Further studies are required to establish whether PEP-breathing prophylactic mechanisms also occur in participants with more severe acute mountain sickness.

Medex 2015: The key role of cardiac mechanics to maintain biventricular function at high altitude.

NEW FINDINGS: What is the central question of this study? This study is the first to investigate the effects of high-altitude trekking on biventricular mechanics, including measurements of left ventricular subendocardial and subepicardial function. What is the main finding and its importance? We provide new evidence that an increased contractility and untwisting efficiency, a key element of diastolic function, probably plays a key role in preservation of cardiac function during high-altitude trekking. Persistent increased loading conditions during several weeks at high altitude might have a key role in the appearance of left or right ventricular dysfunction. ABSTRACT: Cardiac responses to acute hypoxic exposure have been thoroughly investigated. We analysed the effects of high-altitude trekking (i.e. prolonged hypoxic exposure) on biventricular function, including the evaluation of subendocardial and subepicardial function in the left ventricle (LV). Resting evaluations of LV and right ventricular (RV) function and mechanics were assessed by speckle tracking echocardiography on 20 subjects at sea level and at high altitude (5085 m, after a 10 day ascent). Pulmonary artery systolic pressure was increased at high altitude (sea level, 13.1 ± 5.9 mmHg; high altitude, 26.6 ± 10.8 mmHg; P < 0.001). Left ventricular volumes were decreased, whereas RV volumes were increased at high altitude. Alterations in pulmonary artery systolic pressure and cardiac volumes were correlated with hypoxaemia. We observed neither RV nor LV systolic dysfunction, including analysis of LV subendocardial and subepicardial function. Left ventricular systolic strain rates were enhanced at high altitude. Transmitral and transtricuspid diastolic filling ratios were decreased at high altitude. Diastolic apical rotational rate, untwisting rate and untwisting rate/peak twist ratio (i.e. untwisting efficiency) were enhanced at high altitude. We observed no echocardiographic signs of LV and RV pathological dysfunction at rest at high altitude. In contrast, our data highlighted major changes in the LV mechanics, with an increased LV contractility and a higher untwisting efficiency at high altitude. Biventricular interaction, alterations in loading conditions and an increase in plasma catecholamine concentration might partly explain these modifications. Thus, we demonstrated that LV mechanics (i.e. increased strain rates and untwisting efficiency) have a key role in preservation of cardiac function during high-altitude trekking.

Microbeam radiation therapy - grid therapy and beyond: a clinical perspective.

Microbeam irradiation is spatially fractionated radiation on a micrometer scale. Microbeam irradiation with therapeutic intent has become known as microbeam radiation therapy (MRT). The basic concept of MRT was developed in the 1980s, but it has not yet been tested in any human clinical trial, even though there is now a large number of animal studies demonstrating its marked therapeutic potential with an exceptional normal tissue sparing effect. Furthermore, MRT is conceptually similar to macroscopic grid based radiation therapy which has been used in clinical practice for decades. In this review, the potential clinical applications of MRT are analysed for both malignant and non-malignant diseases.

Multiparametric Magnetic Resonance Investigation of Brain Adaptations to 6 Days at 4350 m.

OBJECTIVE: Hypoxic exposure in healthy subjects can induce acute mountain sickness including headache, lethargy, cerebral dysfunction, and substantial cerebral structural alterations which, in worst case, can lead to potentially fatal high altitude cerebral edema. Within this context, the relationships between high altitude-induced cerebral edema, changes in cerebral perfusion, increased brain parenchyma volume, increased intracranial pressure, and symptoms remain unclear. METHODS: In 11 subjects before and after 6 days at 4350 m, we performed multiparametric magnetic resonance investigations including anatomical, apparent diffusion coefficient and arterial spin labeling sequences. RESULTS: After the altitude stay, while subjects were asymptomatic, white matter volume (+0.7 ± 0.4%, p = 0.005), diffusion (+1.7 ± 1.4%, p = 0.002), and cerebral blood flow (+28 ± 38%; p = 0.036) were significantly increased while cerebrospinal fluid volume was reduced (-1.4 ± 1.1%, p = 0.009). Optic nerve sheath diameter (used as an index of increased intracranial pressure) was unchanged from before (5.84 ± 0.53 mm) to after (5.92 ± 0.60 mm, p = 0.390) altitude exposure. Correlations were observed between increases in white matter volume and diffusion (rho = 0.81, p = 0.016) and between changes in CSF volume and changes in ONSD s (rho = -0.92, p = 0.006) and symptoms during the altitude stay (rho = -0.67, p = 0.031). CONCLUSIONS: These data demonstrate white matter alterations after several days at high altitude when subjects are asymptomatic that may represent the normal brain response to prolonged high altitude exposure.

Towards the Design of a Patient-Specific Virtual Tumour.

The design of a patient-specific virtual tumour is an important step towards Personalized Medicine. However this requires to capture the description of many key events of tumour development, including angiogenesis, matrix remodelling, hypoxia, and cell state heterogeneity that will all influence the tumour growth kinetics and degree of tumour invasiveness. To that end, an integrated hybrid and multiscale approach has been developed based on data acquired on a preclinical mouse model as a proof of concept. Fluorescence imaging is exploited to build case-specific virtual tumours. Numerical simulations show that the virtual tumour matches the characteristics and spatiotemporal evolution of its real counterpart. We achieved this by combining image analysis and physiological modelling to accurately described the evolution of different tumour cases over a month. The development of such models is essential since a dedicated virtual tumour would be the perfect tool to identify the optimum therapeutic strategies that would make Personalized Medicine truly reachable and achievable.

Cerebral volumetric changes induced by prolonged hypoxic exposure and whole-body exercise.

The present study assessed the isolated and synergetic effects of hypoxic exposure and prolonged exercise on cerebral volume and subedema and symptoms of acute mountain sickness (AMS). Twelve healthy males performed three semirandomized blinded 11-hour sessions with (1) an inspiratory oxygen fraction (FiO2) of 12% and 4-hour cycling, (2) FiO2=21% and 4-hour cycling, and (3) FiO2=8.5% to 12% at rest (matching arterial oxygen saturation measured during the first hypoxic session). Volumetric, apparent diffusion coefficient (ADC), and arterial spin labelling 3T magnetic resonance imaging sequences were performed after 30 minutes and 10 hours in each session. Thirty minutes of hypoxia at rest induced a significant increase in white-matter volume (+0.8±1.0% compared with normoxia) that was exacerbated after 10 hours of hypoxia at rest (+1.5±1.1%) or with cycling (+1.6±1.1%). Total brain parenchyma volume increased significantly after 10 hours of hypoxia with cycling only (+1.3±1.1%). Apparent diffusion coefficient was significantly reduced after 10 hours of hypoxia at rest or with cycling. No significant change in cerebral blood flow was observed. These results demonstrate changes in white-matter volume as early as after 30 minutes of hypoxia that worsen after 10 hours, probably due to cytotoxic edema. Exercise accentuates the effect of hypoxia by increasing total brain volume. These changes do not however correlate with AMS symptoms.

Absolute perfusion measurements and associated iodinated contrast agent time course in brain metastasis: a study for contrast-enhanced radiotherapy.

Contrast-enhanced radiotherapy is an innovative treatment that combines the selective accumulation of heavy elements in tumors with stereotactic irradiations using medium energy X-rays. The radiation dose enhancement depends on the absolute amount of iodine reached in the tumor and its time course. Quantitative, postinfusion iodine biodistribution and associated brain perfusion parameters were studied in human brain metastasis as key parameters for treatment feasibility and quality. Twelve patients received an intravenous bolus of iodinated contrast agent (CA) (40 mL, 4 mL/s), followed by a steady-state infusion (160 mL, 0.5 mL/s) to ensure stable intratumoral amounts of iodine during the treatment. Absolute iodine concentrations and quantitative perfusion maps were derived from 40 multislice dynamic computed tomography (CT) images of the brain. The postinfusion mean intratumoral iodine concentration (over 30 minutes) reached 1.94 ± 0.12 mg/mL. Reasonable correlations were obtained between these concentrations and the permeability surface area product and the cerebral blood volume. To our knowledge, this is the first quantitative study of CA biodistribution versus time in brain metastasis. The study shows that suitable and stable amounts of iodine can be reached for contrast-enhanced radiotherapy. Moreover, the associated perfusion measurements provide useful information for the patient recruitment and management processes.

Cerebral hemodynamic and ventilatory responses to hypoxia, hypercapnia, and hypocapnia during 5 days at 4,350 m.

This study investigated the changes in cerebral near-infrared spectroscopy (NIRS) signals, cerebrovascular and ventilatory responses to hypoxia and CO2 during altitude exposure. At sea level (SL), after 24 hours and 5 days at 4,350 m, 11 healthy subjects were exposed to normoxia, isocapnic hypoxia, hypercapnia, and hypocapnia. The following parameters were measured: prefrontal tissue oxygenation index (TOI), oxy- (HbO2), deoxy- and total hemoglobin (HbTot) concentrations with NIRS, blood velocity in the middle cerebral artery (MCAv) with transcranial Doppler and ventilation. Smaller prefrontal deoxygenation and larger ΔHbTot in response to hypoxia were observed at altitude compared with SL (day 5: ΔHbO2-0.6±1.1 versus -1.8±1.3 µmol/cmper mm Hg and ΔHbTot 1.4±1.3 versus 0.7±1.1 µmol/cm per mm Hg). The hypoxic MCAv and ventilatory responses were enhanced at altitude. Prefrontal oxygenation increased less in response to hypercapnia at altitude compared with SL (day 5: ΔTOI 0.3±0.2 versus 0.5±0.3% mm Hg). The hypercapnic MCAv and ventilatory responses were decreased and increased, respectively, at altitude. Hemodynamic responses to hypocapnia did not change at altitude. Short-term altitude exposure improves cerebral oxygenation in response to hypoxia but decreases it during hypercapnia. Although these changes may be relevant for conditions such as exercise or sleep at altitude, they were not associated with symptoms of acute mountain sickness.

Photoactivation of gold nanoparticles for glioma treatment.

Radiosensitization efficacy of gold nanoparticles (AuNPs) with low energy radiations (88 keV) was evaluated in vitro and in vivo on rats bearing glioma. In vitro, a significant dose-enhancement factor was measured by clonogenic assays after irradiation with synchrotron radiation of F98 glioma cells in presence of AuNPs (1.9 and 15 nm in diameter). In vivo, 1.9 nm nanoparticles were found to be toxic following intracerebral delivery in rats bearing glioma, whether no toxicity was observed using 15 nm nanoparticles at the same concentration (50 mg/mL). The therapeutic efficacy of gold photoactivation was determined by irradiating the animals after intracerebral infusion of AuNPs. Survival of rats that had received the combination of treatments (AuNPs: 50 mg/mL, 15 Gy) was significantly increased in comparison with the survival of rats that had received irradiation alone. In conclusion, this experimental approach is promising and further studies are foreseen for improving its therapeutic efficacy. FROM THE CLINICAL EDITOR: These investigators report that gold nanoparticles of the correct size can be used to enhance the effects of irradiation in the context of a glioma model. Since many of the glioma varieties are currently incurable, this or similar approaches may find their way to clinical trials in the near future.

On the normalization of cerebral blood flow.

Cerebral blood flow (CBF) is the most common parameter for the quantification of brain's function. Literature data indicate a widespread dispersion of values that might be related to some differences in the measurement conditions that are not properly taken into account in CBF evaluation. Using recent high-resolution imaging of the complete cortical microvasculature of primate brain, we perform extensive numerical evaluation of the cerebral perfusion. We show that blood perfusion associated with intravascular tracers should be normalized by the surface of the voxel rather than by its volume and we consistently test this result on the available literature data.

Changes in cerebral blood flow and vasoreactivity to CO2 measured by arterial spin labeling after 6days at 4350m.

Changes in cerebral perfusion and CO2 cerebrovascular reactivity during and immediately after a sojourn at high altitude remain unclear but may be critical for acclimatization. The aim of the present study was to assess the effects of 6days at 4350m on cerebral perfusion and cerebrovascular reactivity (CVR) to CO2 by arterial spin labeling (ASL) magnetic resonance imaging at sea level and to compare it with transcranial Doppler (TCD) results at altitude. Eleven healthy male subjects, non-acclimatized to altitude, stayed for 6days at 4350m (Observatoire Vallot, massif du Mont-Blanc). Prior to the stay and within 6h after returning to sea level, subjects were investigated using pseudo-continuous ASL at 3T during a block-design inhalation paradigm to measure basal cerebral blood flow (CBF) and CO2 CVR. End-tidal CO2 (PetCO2), respiratory rate, heart rate and oxygen saturation were recorded during the exam. Subjects were also examined using TCD prior to and on day 5 of the stay at altitude to measure blood velocity in the middle cerebral artery (MCAv) and CO2 CVR. CO2 CVR was expressed as percent change in ASL CBF or TCD MCAv per mmHg change in PetCO2. PetCO2 was significantly decreased during and after altitude. Significant increases in TCD MCAv compared to before altitude measurements were observed on day 5 at altitude (+20.5±15.5%). Interestingly, ASL CBF remained increased in the MCA and anterior vascular territories (+22.0±24.1% and 20.5±20.3%, respectively) after altitude under normoxic conditions. TCD CVR tended to decrease on day 5 at 4350m (-12.3±54.5% in the MCA) while the ASL CVR was significantly decreased after altitude (-29.5±19.8% in the MCA). No correlation was observed between cerebral hemodynamic changes and symptoms of acute mountain sickness at high altitude. In conclusion, prolonged exposure to high altitude significantly increases blood flow during the altitude stay and within 6h after returning to sea level. Decreased CO2 CVR after prolonged altitude exposure was also observed using ASL. Changes in cerebral hemodynamics with altitude exposure probably involve other mechanisms than the vasodilatory effect of hypoxia only, since it persists under normoxia several hours following the descent.

The effect of hypoxemia and exercise on acute mountain sickness symptoms.

Performing exercise during the first hours of hypoxic exposure is thought to exacerbate acute mountain sickness (AMS), but whether this is due to increased hypoxemia or other mechanisms associated with exercise remains unclear. In 12 healthy men, AMS symptoms were assessed during three 11-h experimental sessions: 1) in Hypoxia-exercise, inspiratory O(2) fraction (Fi(O(2))) was 0.12, and subjects performed 4-h cycling at 45% Fi(O(2))-specific maximal power output from the 4th to the 8th hour; 2) in Hypoxia-rest, Fi(O(2)) was continuously adjusted to match the same arterial oxygen saturation as in Hypoxia-exercise, and subjects remained at rest; and 3) in Normoxia-exercise, Fi(O(2)) was 0.21, and subjects cycled as in Hypoxia-exercise at 45% Fi(O(2))-specific maximal power output. AMS scores did not differ significantly between Hypoxia-exercise and Hypoxia-rest, while they were significantly lower in Normoxia-exercise (Lake Louise score: 5.5 ± 2.1, 4.4 ± 2.4, and 2.3 ± 1.5, and cerebral Environmental Symptom Questionnaire: 1.2 ± 0.7, 1.0 ± 1.0, and 0.3 ± 0.4, in Hypoxia-exercise, Hypoxia-rest, and Normoxia-exercise, respectively; P < 0.01). Headache scored by visual analog scale was higher in Hypoxia-exercise and Hypoxia-rest compared with Normoxia-exercise (36 ± 22, 35 ± 25, and 5 ± 6, P < 0.001), while the perception of fatigue was higher in Hypoxia-exercise compared with Hypoxia-rest (60 ± 24, 32 ± 22, and 46 ± 23, in Hypoxia-exercise, Hypoxia-rest, and Normoxia-exercise, respectively; P < 0.01). Despite significant physiological stress during hypoxic exercise and some AMS symptoms induced by normoxic cycling at similar relative workload, exercise does not significantly worsen AMS severity during the first hours of hypoxic exposure at a given arterial oxygen desaturation. Hypoxemia per se appears, therefore, to be the main mechanism underlying AMS, whether or not exercise is performed.

Synchrotron X-ray interlaced microbeams suppress paroxysmal oscillations in neuronal networks initiating generalized epilepsy.

Radiotherapy has shown some efficacy for epilepsies but the insufficient confinement of the radiation dose to the pathological target reduces its indications. Synchrotron-generated X-rays overcome this limitation and allow the delivery of focalized radiation doses to discrete brain volumes via interlaced arrays of microbeams (IntMRT). Here, we used IntMRT to target brain structures involved in seizure generation in a rat model of absence epilepsy (GAERS). We addressed the issue of whether and how synchrotron radiotherapeutic treatment suppresses epileptic activities in neuronal networks. IntMRT was used to target the somatosensory cortex (S1Cx), a region involved in seizure generation in the GAERS. The antiepileptic mechanisms were investigated by recording multisite local-field potentials and the intracellular activity of irradiated S1Cx pyramidal neurons in vivo. MRI and histopathological images displayed precise and sharp dose deposition and revealed no impairment of surrounding tissues. Local-field potentials from behaving animals demonstrated a quasi-total abolition of epileptiform activities within the target. The irradiated S1Cx was unable to initiate seizures, whereas neighboring non-irradiated cortical and thalamic regions could still produce pathological oscillations. In vivo intracellular recordings showed that irradiated pyramidal neurons were strongly hyperpolarized and displayed a decreased excitability and a reduction of spontaneous synaptic activities. These functional alterations explain the suppression of large-scale synchronization within irradiated cortical networks. Our work provides the first post-irradiation electrophysiological recordings of individual neurons. Altogether, our data are a critical step towards understanding how X-ray radiation impacts neuronal physiology and epileptogenic processes.

Intracerebral delivery of carboplatin in combination with either 6 MV photons or monoenergetic synchrotron X-rays are equally efficacious for treatment of the F98 rat glioma.

BACKGROUND: The purpose of the present study was to compare side-by-side the therapeutic efficacy of a 6-day infusion of carboplatin, followed by X-irradiation with either 6 MV photons or synchrotron X-rays, tuned above the K-edge of Pt, for treatment of F98 glioma bearing rats. METHODS: Carboplatin was administered intracerebrally (i.c.) to F98 glioma bearing rats over 6 days using AlzetTM osmotic pumps starting 7 days after tumor implantation. Radiotherapy was delivered in a single 15 Gy fraction on day 14 using a conventional 6 MV linear accelerator (LINAC) or 78.8 keV synchrotron X-rays. RESULTS: Untreated control animals had a median survival time (MeST) of 33 days. Animals that received either carboplatin alone or irradiation alone with either 78.8 keV or 6 MV had a MeSTs 38 and 33 days, respectively. Animals that received carboplatin in combination with X-irradiation had a MeST of > 180 days with a 55% cure rate, irrespective of whether they were irradiated with either 78.8 KeV synchrotron X-rays or 6MV photons. CONCLUSIONS: These studies have conclusively demonstrated the equivalency of i.c. delivery of carboplatin in combination with X-irradiation with either 6 MV photons or synchrotron X-rays.

Ventilatory responses to exercise training in obese adolescents.

The aim of this study was to examine ventilatory responses to training in obese adolescents. We assessed body composition, pulmonary function and ventilatory responses (among which expiratory flow limitation and operational lung volumes) during progressive cycling exercise in 16 obese adolescents (OB) before and after 12 weeks of exercise training and in 16 normal-weight volunteers. As expected, obese adolescents' resting expiratory reserve volume was lower and inversely correlated with thoraco-abdominal fat mass (r = -0.74, p<0.0001). OB presented lower end expiratory (EELV) and end inspiratory lung volumes (EILV) at rest and during submaximal exercise, and modest expiratory flow limitation. After training, OB increased maximal aerobic performance (+19%) and maximal inspiratory pressure (93.7±31.4 vs. 81.9±28.2 cm H2O, +14%) despite lack of decrease in trunk fat and body weight. Furthermore, EELV and EILV were greater during submaximal exercise (+11% and +9% in EELV and EILV, respectively), expiratory flow limitation delayed but was not accompanied by increased V(T). However, submaximal exertional symptoms (dyspnea and leg discomfort) were significantly decreased (-71.3% and -70.7%, respectively). Our results suggest that exercise training can improve pulmonary function at rest (static inspiratory muscle strength) and exercise (greater operating lung volumes and delayed expiratory flow limitation) but these modifications did not entirely account for improved dyspnea and exercise performance in obese adolescents.